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Aging Phenotype (aging + phenotype)

Distribution by Scientific Domains

Medical Sciences	50%

Selected Abstracts

Proteomic profiling reveals a catalogue of new candidate proteins for human skin aging

EXPERIMENTAL DERMATOLOGY, Issue 10 2010
Martin Laimer
Abstract:, Studies of skin aging are usually performed at the genomic level by investigating differentially regulated genes identified through subtractive hybridization or microarray analyses. In contrast, relatively few studies have investigated changes in protein expression of aged skin using proteomic profiling by two-dimensional (2-D) gel electrophoresis and mass spectrometry, although this approach at the protein level is suggested to reflect more accurately the aging phenotype. We undertook such a proteomic analysis of intrinsic human skin aging by quantifying proteins extracted and fluorescently labeled from sun-protected human foreskin samples pooled from ,young' and ,old' men. In addition, we analyzed these candidate gene products by 1-D and 2-D western blotting to obtain corroborative protein expression data, and by both real-time PCR (RT-PCR) and microarray analyses to confirm expression at the mRNA level. We discovered 30 putative proteins for skin aging, including previously unrecognized, post-translationally regulated candidates such as phosphatidyl-ethanolamine binding protein (PEBP) and carbonic anhydrase 1 (CA1). [source]

Multiple pathology and tails of disability: Space,time structure of disability in longevity

GERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 4 2003
Satoru Matsushita
Disability and the resulting lowered quality of life are serious issues accompanying increased longevity. Curiously, despite its potential contribution to aging theory, complete statistical and etiological structures of this common and unwelcome aging phenotype before death have not been well identified. Another neglected issue in aging and disability is the principles of phylogenesis and morphogenesis, which contemporary life science invariably starts with. In the present review these two related subjects are addressed, with an introduction of an analysis on patients and published data. Statistically rigorous log,normal and normal distributions distinguish disability for its duration and age-wise distribution, respectively. Multiple pathology and diverse effects of various endogenous diseases on disability are confirmed. The robust long-tailed log,normal distribution for various phases of disability validates the fact that patients in disability undergo series of stochastic subprocesses of many independent endogenous diseases until death. For 60% of patients, the log,normal distribution is mimicked by a random walk model. Diseases of core organs are major causes of the long tails. A declining force of natural selection after reproduction and trade-off of life history through pleiotropy of the genes are considered to be the roots of aging. The attenuated selection pressure and the resulting decrease of genetic constraints produce an increased opportunity for chance and stochastics. Elucidated stochastic behaviors of disability underscore the key role of chance in aging. Evolutionary modifications in the development of the structure tend to favor developmentally later stages first. Distal parts are developmentally last, therefore most subject to modification. The rate of molecular evolution of the genes is also found to be relatively slow at the core and rapid at the edge of cells and organs. Therefore, systems at the core must be relatively slow and inactive to comply with pleiotropy and trade-offs in comparison with systems at the edge. Hence, against flat and probabilistic aging, the core organs must be moulded to be more robust with a lower threshold for dysfunction, to age relatively slowly, and should have less of a disease quota in aging. The principle of core protective aging assures possibilities not only to reduce disability but also to accomplish the Third Age as well. Finally, it must also be acknowledged that the principle is a double-edged sword. Paradoxically, the developed biological and societal organization provides protection for the injured core, and so develops long tails of disability. The principle of core protective aging re-emphasizes the key role of prevention in order to reduce the amount of disability. [source]

MicroRNA regulation in Ames dwarf mouse liver may contribute to delayed aging

AGING CELL, Issue 1 2010
David J. Bates
Summary The Ames dwarf mouse is well known for its remarkable propensity to delay the onset of aging. Although significant advances have been made demonstrating that this aging phenotype results primarily from an endocrine imbalance, the post-transcriptional regulation of gene expression and its impact on longevity remains to be explored. Towards this end, we present the first comprehensive study by microRNA (miRNA) microarray screening to identify dwarf-specific lead miRNAs, and investigate their roles as pivotal molecular regulators directing the long-lived phenotype. Mapping the signature miRNAs to the inversely expressed putative target genes, followed by in situ immunohistochemical staining and in vitro correlation assays, reveals that dwarf mice post-transcriptionally regulate key proteins of intermediate metabolism, most importantly the biosynthetic pathway involving ornithine decarboxylase and spermidine synthase. Functional assays using 3,-untranslated region reporter constructs in co-transfection experiments confirm that miRNA-27a indeed suppresses the expression of both of these proteins, marking them as probable targets of this miRNA in vivo. Moreover, the putative repressed action of this miRNA on ornithine decarboxylase is identified in dwarf mouse liver as early as 2 months of age. Taken together, our results show that among the altered aspects of intermediate metabolism detected in the dwarf mouse liver , glutathione metabolism, the urea cycle and polyamine biosynthesis , miRNA-27a is a key post-transcriptional control. Furthermore, compared to its normal siblings, the dwarf mouse exhibits a head start in regulating these pathways to control their normality, which may ultimately contribute to its extended healthspan and longevity. [source]

SIRT6 protects against pathological damage caused by diet-induced obesity

AGING CELL, Issue 2 2010
Yariv Kanfi
Summary The NAD+-dependent SIRT6 deacetylase is a therapeutic candidate against the emerging metabolic syndrome epidemic. SIRT6, whose deficiency in mice results in premature aging phenotypes and metabolic defects, was implicated in a calorie restriction response that showed an opposite set of phenotypes from the metabolic syndrome. To explore the role of SIRT6 in metabolic stress, wild type and transgenic (TG) mice overexpressing SIRT6 were fed a high fat diet. In comparison to their wild-type littermates, SIRT6 TG mice accumulated significantly less visceral fat, LDL-cholesterol, and triglycerides. TG mice displayed enhanced glucose tolerance along with increased glucose-stimulated insulin secretion. Gene expression analysis of adipose tissue revealed that the positive effect of SIRT6 overexpression is associated with down regulation of a selective set of peroxisome proliferator-activated receptor-responsive genes, and genes associated with lipid storage, such as angiopoietin-like protein 4, adipocyte fatty acid-binding protein, and diacylglycerol acyltransferase 1, which were suggested as potential targets for drugs to control metabolic syndrome. These results demonstrate a protective role for SIRT6 against the metabolic consequences of diet-induced obesity and suggest a potentially beneficial effect of SIRT6 activation on age-related metabolic diseases. [source]